Possible genetic predisposition to lymphedema after breast cancer

Background: Known risk factors for secondary lymphedema only partially explain who develops lymphedema following cancer, suggesting that inherited genetic susceptibility may influence risk. Moreover, identification of molecular signatures could facilitate lymphedema risk prediction prior to surgery or lead to effective drug therapies for prevention or treatment. Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema. Methods and Results: We undertook a nested case-control study, with participants who had developed lymphedema after surgical intervention within the first 18 months of their breast cancer diagnosis serving as cases (n=22) and those without lymphedema serving as controls (n=98), identified from a prospective, population-based, cohort study in Queensland, Australia. TagSNPs that covered all known genetic variation in the genes SOX18, VEGFC, VEGFD, VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM and PROX1 were selected for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3 and RORC, were associated with lymphedema defined by statistical significance (p<0.05) or extreme risk estimates (OR<0.5 or >2.0). Conclusions: These provocative, albeit preliminary, findings regarding possible genetic predisposition to secondary lymphedema following breast cancer treatment warrant further attention for potential replication using larger datasets.

Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

The experience of being an advanced practice nurse within Australian acute care settings : a systematic review of qualitative evidence

Background There is a vast amount of international literature which, although agreeing on the need for advanced practice nurse roles, simultaneously debates and discusses the difficulties with nomenclature, definition and subsequent implementation of such roles. Due to this ambiguity it is difficult to equally compare evidence in this field across different countries. A context-specific systematic review on the qualitative evidence of the experience of being an advanced practice nurse in Australia has not been undertaken previously, however it is imperative for nursing managers and leaders to understand the complexities of advanced nursing roles in order to effectively utilise and retain these experienced and valuable nurses. With the creation of a national nursing regulating authority in 2010, it is timely to explore in-depth the experience of being an advanced practice nurse from a national perspective. Objective To identify the experience of being an advanced practice nurse working in Australian acute care settings. Inclusion criteria -Types of participants Registered nurses working in advanced practice roles in acute care settings throughout Australia. -Phenomena of interest The experience of being an advanced practice registered nurse working in an Australian acute care setting, as reported by the nurses themselves. -Types of studies Interpretive qualitative studies including designs such as phenomenology, grounded theory and ethnography. -Search strategy A three step search strategy was used to identify published and unpublished studies. The search process was conducted from August to October 2011 and considered published and unpublished studies from 1990 to October 2011. -Methodological quality Studies were appraised for methodological quality by two independent reviewers using the Joanna Briggs Qualitative Assessment and Review Instrument. -Data extraction Data was extracted from the papers included in the review using the standardised Joanna Briggs Institute Qualitative Assessment and Review Instrument data extraction tool. -Data synthesis Research findings were pooled using the Joanna Briggs Institute Qualitative Data and Review Instrument. Results Three published studies and one unpublished dissertation were included in the review. From these four studies, 216 findings were extracted, forming 18 categories which were then analysed to create six synthesised findings. Six meta-syntheses under the headings of expert knowledge, confidence, education, relationships, negative experiences and patient centred experience were formed from the findings. Conclusions The synthesised findings confirm that the experience of advanced practice nurses in Australian acute care settings is complex and greatly influenced personally and professionally by the organisation as well as the unpredictable nature of working with people.

Experience of being an advanced practice nurse within Australian acute care settings : a systematic review of qualitative evidence

Background Nationally and internationally, advanced practice nurses are working under various titles and in different contexts to address gaps within healthcare systems. Analysis of advanced practice roles in different countries has been undertaken, but due to variations in cultural, geographical and professional factors, it is difficult and perhaps ineffectual to compare roles between countries. Contextual factors may also affect the actual experience of being an advanced practice nurse. A systematic review was therefore undertaken of qualitative evidence on the experience of being an advanced practice nurse in Australia, to provide deeper understanding of the role in the defined context. Methods The review followed the method for qualitative synthesis as per the Joanna Briggs Institute. An extensive search was undertaken of databases and online resources to find published and unpublished studies. Papers from 1990 to October 2011 which met specified inclusion criteria were appraised using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Results Three published studies and one unpublished dissertation were included in the review. From these studies, 216 findings were extracted and these were formed into 18 categories. Six meta-syntheses grouped under the headings of expert knowledge, confidence, education, relationships, negative experiences and patient-centred experience were created. Organisational factors impact greatly on the experience, professionally and personally. Conclusions Heterogeneity of role titles makes synthesis a difficult process, but contextualising the population provides a pragmatic approach to informing the status of the advanced practice nurse discourse. The review identifies positive and negative experiences of being an advanced practice nurse in Australian acute care settings with overlapping and intertwining findings that reinforce the complexity of the role.

Patient perspectives of using a web based intervention program for patients with type 2 diabetes and acute coronary syndrome

Introduction Research highlights patients with dual diagnoses of type 2 diabetes and acute coronary syndrome (ACS) have higher readmission rates and poorer health outcomes than patients with singular chronic conditions. Despite this, there is a lack of education programs targeted for this dual diagnosis population to improve self-management and decrease negative health outcomes. There is evidence to suggest that internet based interventions may improve health outcomes for patients with singular chronic conditions, however there is a need to develop an evidence base for ACS patients with comorbid diabetes. There is a growing awareness of the importance of a participatory model in developing effective online interventions. That is, internet interventions are more effective if end users’ perceptions of the intervention are incorporated in their final development prior to testing in large scale trials. Objectives This study investigated patients’ perspectives of the web-based intervention designed to promote self-management of the dual conditions in order to refine the intervention prior to clinical trial evaluation. Methods An interpretive approach with thematic analysis was used to obtain deeper understanding regarding participants’ experience when using web-application interventions for patients with ACS and type 2 diabetes. Semi-structured interviews were undertaken on a purposive sample of 30 patients meeting strict inclusion and exclusion criteria to obtain their perspectives on the program. Results Preliminary results indicate patients with dual diagnoses express more complex needs than those with a singular condition. Participants express a positive experience with the proposed internet intervention and emerging themes include that the web page is seen as easy to use and comforting as a support, in that patients know they are not alone. Further results will be reported as they become available. Conclusion The results indicate potential for patient acceptability of the newly developed internet intervention for patients with ACS and comorbid diabetes. Incorporation of patient perspectives into the final development of the intervention is likely to maximise successful outcomes of any future trials that utilise this intervention. Future quantitative evaluation of the effectiveness of the intervention is being planned.

Strategies for teaching evidence-based practice to undergraduate health students: A systematic review protocol

Review question/objective The objective of this review is to find, critically appraise and synthesize the available quantitative evidence on the effectiveness of interventions that promote successful teaching of the evidence-based practice process in undergraduate health students, in preparation for them to become professional evidence-based practitioners. More specifically, the question that this review seeks to answer is: What is the effectiveness of teaching strategies for evidence-based practice for undergraduate health students? Inclusion criteria Types of participants This review will consider studies that include undergraduate health students from any undergraduate health discipline, including but not limited to medicine, nursing and allied health. Post graduate and post-registration students will not be included. Types of interventions This review will consider studies that evaluate strategies or interventions aimed at teaching any or all of the five steps of evidence-based practice, namely asking a structured clinical question; collecting the best evidence available; critically appraising the evidence to ensure validity, relevance and applicability; applying or integrating the results into clinical practice, and evaluating outcomes. The strategy may take place solely within a tertiary education environment or may be combined with a clinical setting. Types of outcomes This review will consider studies that include the following outcome measures: evidence-based practice behavior, knowledge, skills, attitudes, self-efficacy (or self-confidence), beliefs, values, intention to use evidence-based practice (future use) and confidence levels. Tools used to measure these outcomes will be assessed for reported validity, reliability and generalizability. Outcomes will be measured during the student’s education period up to graduation. If studies are conducted across different year levels this will be taken into account during analysis and reported accordingly.

The effectiveness of psychosocial interventions for cognitive dysfunction in cancer patients who have received chemotherapy : a systematic review

Background: Chemotherapy-related cognitive dysfunction (CRCD) refers to problems with memory,attention span, or concentration, experienced by patients with cancer who have had chemotherapy. CRCD can have a significant negative effect on a patient’s quality of life. The exact cause of CRCD is unknown but is presumed to be multifactorial. Objective: To conduct a systematic review of the effectiveness of psychosocial interventions designed to treat CRCD. Methods: Participants of interest to the review were over 18 years of age, diagnosed with cancer, and receiving chemotherapy or had received chemotherapy in the past. Interventions of interest were methods to improve cognitive function. Included study designs were randomized controlled trials, quasi-experimental trials, and quantitative observational studies. The primary outcome of interest was level of cognitive function. A three-step search strategy was utilized to identify studies published from 1985 to 2011 from a wide range of databases. Joanna Briggs Institute systematic review methods were used but findings were analyzed using the Cochrane Collaboration Review Manager 5.1 program.Weightedmean differences with 95% confidence intervals were calculated from the continuous data. Results: Searching identified 3,109 potentially relevant articles and 120 full-text articles were retrieved. Two further papers were sourced from reference lists of retrieved articles. From 122 papers, six were suitable for critical appraisal and six were included in the analysis. Meta-analysis was conducted on two cognitive behavioral therapy (CBT) trials for the outcome of inability to concentrate. Significant effect was seen for one CBT intervention at 20 weeks (p = .004). Significant effect from CBT on quality of life was seen at 6-month follow-up (p < .05). Conclusions: Despite some evidence of an effect, there is insufficient evidence at this stage to strongly recommend any of the interventions to assist in decreasing the effects of CRCD, except in terms of improving quality of life.